In vivo and in vitro inhibition of nicosulfuron metabolism by terbufos metabolites in maize

Reduced maize tolerance to nicosulfuron [2-(((((4,6-dimethyoxy-2-pyrimidinyl)amino)carbonyl)amino)sulfonyl)-N, N-dimethyl-3-pyridinecarboxamide], a sulfonylurea herbicide, occurred when the herbicide was applied following terbufos (S-[[(1,1-dimethylethyl)thio]methyl]O, O-diethyl phosphorodithioate) insecticide. To determine the mechanism of this interaction, the effect of terbufos on the metabolism of nicosulfuron was studied in whole plants and in an in vitro microsomal system from maize. Terbufos applied in the nutrient solution of hydroponically grown maize 36 hr prior to herbicide application increased nicosulfuron uptake 4% 48 hr after treatment. Nicosulfuron metabolism decreased by 10 and 15%, respectively, for the 0.45 and 4.5 µM terbufos treatments 24 hr after application. Plants grown in the presence of the terbufos oxidative metabolites, terbufos-sulfoxide (phosphorodithioic acid S-[(tert-butylsulfinyl)methyl]O, O-diethyl ester) and terbufos-sulfone (phosphorodithioic acid S-[[(1,1-dimethylethyl)sulfonyl]methyl]O, O-diethyl ester), had 22 and 55% reductions in nicosulfuron metabolism, respectively, at 24 hr after herbicide application. In microsomal preparations, terbufos-SO and terbufos-SF severely inhibited cytochrome P450 mediated hydroxylation of nicosulfuron while terbufos had a lesser effect. Terbufos-SF was more inhibitory in vitro than terbufos-SO. Terbufos-SO and terbufos-SF reduced nicosulfuron tolerance in maize by inhibiting the cytochrome P450 monooxygenases involved in nicosulfuron hydroxylation.